Chlamydia psittaci: a relevant cause of community-acquired pneumonia in two Dutch hospitals.

BACKGROUND: Of all hospitalised community-acquired pneumonias (CAPs) only a few are known to be caused by Chlamydia psittaci. Most likely the reported incidence, ranging from of 0% to 2.1%, is an underestimation of the real incidence, since detection of psittacosis is frequently not incorporated in the routine microbiological diagnostics in CAP or serological methods are used. METHODS: C. psittaci real-time polymerase chain reaction (PCR) was routinely performed on the sputum of 147 patients hospitalised with CAP, who participated in a clinical trial conducted in two Dutch hospitals. In 119/147 patients the paired complement fixation test (CFT) was also performed for the presence of Chlamydia antibodies. Positive CFTs were investigated by micro- Immunofluorescence for psittacosis specificity. Case criteria for psittacosis were a positive PCR or a fourfold rise of antibody titre in CFT confirmed by micro- Immunofluorescence. Furthermore, we searched for parameters that could discriminate psittacosis from CAPs with other aetiology. RESULTS: 7/147 (4.8%) patients were diagnosed with psittacosis: six with PCR and one patient with a negative PCR, but with CFT confirmed by micro- Immunofluorescence. Psittacosis patients had had a higher temperature (median 39.6 vs. 38.2 °C;) but lower white blood cell count (median 7.4 vs. 13.7 x 109/l) on admission compared with other CAP patients. CONCLUSION: In this study, C. psittaci as CAP-causing pathogen was much higher than previously reported. To detect psittacosis, PCR was performed on all CAP patients for whom a sputum sample was available. For clinical use, PCR is a fast method and sputum availability allows genotyping; additional serology can optimise epidemiological investigations.

Immunoglobulin A in serum: an old acquaintance as a new prognostic biomarker in idiopathic pulmonary fibrosis.

Immunoglobulin (Ig)A is an important immunoglobulin in mucosal immunity and protects the lungs against invading pathogens. The production of IgA is regulated by transforming growth factor (TGF)-ß, a versatile cytokine and key player in the pathogenesis of pulmonary fibrosis. TGF-ß is up-regulated in patients with idiopathic pulmonary fibrosis (IPF), but difficult to use as a biomarker. The aim of this study was to evaluate the prognostic value of IgA in serum in patients with IPF. We examined IgA levels at time of diagnosis in 86 patients diagnosed with IPF. Mean serum IgA level in IPF is 3·22 g/l and regression analyses showed a significant association with mortality (hazard ratio = 1·445, P = 0·002). A significantly worse survival was found in patients with IgA serum levels > 2·85 g/l compared to patients with lower IgA serum levels (P = 0·003). These findings were confirmed in a duplication cohort. In conclusion, the level of IgA in blood is a promising prognostic marker in IPF and can be implemented easily in the hospital setting. Future studies are warranted to investigate if repeated measurements of serum IgA can further improve the performance of serum IgA as a prognostic marker.

Response to pneumococcal vaccination in mannose-binding lectin-deficient adults with recurrent respiratory tract infections.

Mannose-binding lectin (MBL)-deficiency is associated with an increased susceptibility to pneumococcal infections and other forms of disease. Pneumococcal vaccination is recommended in MBL-deficient patients with recurrent respiratory tract infections (RRTI). The response to pneumococcal vaccination in MBL-deficient individuals has not yet been studied in detail. An impaired response to pneumococcal polysaccharides in MBL-deficient patients might explain the association between MBL deficiency and pneumococcal infections. This study investigates the antibody response to pneumococcal vaccination in MBL-deficient adult patients with RRTI. Furthermore, we investigated whether there was a difference in clinical presentation between MBL-deficient and -sufficient patients with RRTI. Eighteen MBL-deficient and 63 MBL-sufficient adult patients with RRTI were all vaccinated with the 23-valent pneumococcal polysaccharide vaccine and antibodies to 14 pneumococcal serotypes were measured on a Luminex platform. There were no differences observed in the response to pneumococcal vaccination between MBL-sufficient and -deficient patients. Forty-three MBL-sufficient patients could be classified as responders to pneumococcal vaccination and 20 as low responders, compared to 15 responders and three low responders in the MBL-deficient patients. We found no clear difference in clinical, radiological, lung function and medication parameters between MBL-sufficient and -deficient patients. In conclusion, our study suggests that MBL-deficient adults with RRTI have a response to a pneumococcal capsular polysaccharide vaccine comparable with MBL-sufficient patients. Moreover, we did not find a clear clinical role of MBL deficiency in adults with RRTI. As MBL deficiency is associated with an increased susceptibility to pneumococcal infections, pneumococcal vaccination might be protective in MBL-deficient patients with RRTI.

Bronchoalveolar lavage cell pattern from healthy human lung.

Bronchoalveolar lavage (BAL) is widely accepted as a key diagnostic procedure in interstitial lung diseases (ILD). We performed a study to obtain reference intervals of differential cell patterns in BAL fluid with special attention to the origin of lavage fluid, e.g. bronchial/alveolar, to atopy and smoking status and to age of the healthy people. We performed bronchoalveolar lavage in 55 healthy subjects with known atopy status (age: 18-64 years, non-smokers/smokers: 34/21) and determined differential cell counts and lymphocyte subsets in BAL fluid and blood. Moreover, in a subgroup of non-smoking healthy individuals we measured the expression of the regulatory T cell marker forkhead box protein 3 (FoxP3) on blood and BAL fluid lymphocytes in addition to a comprehensive set of activation markers. Differential cell counts from the alveolar lavage fraction differed significantly from calculated pooled fractions (n = 11). In contrast, marginal differences were found between atopic and non-atopic subjects. Interestingly, the BAL fluid CD4(+) /CD8(+) ratio correlated strongly with age (r(2) = 0·50, P < 0·0001). We consider the bronchial and alveolar fraction to be lavage fluid from fundamentally different compartments and recommend analysis of the alveolar fraction in diagnostic work-up of ILD. In addition, our data suggest that age corrected BAL fluid CD4(+) /CD8(+) ratios should be used in the clinical evaluation of patients with interstitial lung diseases.

Systemic cytokine response in patients with community-acquired pneumonia.

The role of individual cytokines and polymorphisms in pneumonia has been described, but the relationship between different cytokines and polymorphisms in relation to causative microorganisms, antibiotics, corticosteroids and clinical course has not. This study questions the relationship between cytokines, polymorphisms and clinical characteristics of pneumonia. Patients diagnosed with pneumonia were included in the study. Serum cytokine levels were measured during hospital stay, genotyping was performed, causative microorganisms were identified and patients were monitored throughout the hospital stay. In 201 patients with pneumonia interleukin (IL)-1 receptor antagonist (IL-1RA), IL-6, IL-8 and IL-10 acted as acute phase proteins. After admission, the levels of these cytokines decreased rapidly. Single nucleotide polymorphisms did not influence cytokine production and were not associated with clinical outcome. Cytokine serum levels were significantly higher in patients with pneumococcal pneumonia. The decrease in levels of cytokines was independently influenced by the start of corticosteroid therapy. IL-1RA, IL-6, IL-8 and IL-10 are acute phase proteins, independent of genotype. Their levels are influenced by the nature of the causative microorganism and the start of corticosteroids therapy.

Impaired antibody response to conjugated meningococcal serogroup C vaccine in asplenic patients.

The purpose of this study was to determine the quantity and quality of antibodies against the meningococcal serogroup C (MenC) conjugated vaccine in asplenic patients. In 116 asplenic patients, antibody concentrations (IgG) were measured against meningococcal serogroup C before and after immunisation. Of MenC-specific IgG, both antibody avidity and subclasses of IgG1 and IgG2 were determined. The mean MenC IgG concentration rose from 0.16 µg/mL prior to vaccination to 3.69 µg/mL 3 weeks post-vaccination, with 67% of patients reaching the threshold of ≥ 2.0 µg/mL. The mean IgG concentration at 35 weeks post-vaccination was 3.10 µg/mL. IgG2 concentrations increased more than IgG1. Marginal avidity maturation was seen. Hypo-responders to the first MenC vaccine (IgG anti-MenC ≤ 2.0 µg/mL) were offered a booster dose. After revaccination, 59% reached the chosen IgG threshold. The IgG concentration rose from 0.29 to 1.12 µg/mL, with an increase in the IgG1/IgG2 ratio. Avidity indices remained below 33%. In asplenic patients, the quantity and quality of antibodies produced after one dose of conjugated MenC vaccination is lower than that observed in previous studies in healthy adults. Booster vaccination does, indeed, lead to a rise in IgG geometric mean concentrations (GMCs), but does not lead to higher avidity of antibodies.

Response to conjugate pneumococcal and Haemophilus influenzae type b vaccines in asplenic patients.

We determined the immunogenicity of conjugated Haemophilus influenzae type b and pneumococcal vaccines by quantitative analysis of the antibody response in asplenic patients. To that end, we vaccinated 92 patients with a conjugated Hib vaccine and 54 received two doses of conjugated pneumococcal vaccine (PCV7), followed at six months by a plain polysaccharide pneumococcal vaccine (PPV23). Antibody concentrations were measured before and three weeks after vaccination. After one dose of pneumococcal conjugate vaccine, 46% of the patients reached the antibody threshold of ≥ 1.0 µg/mL for all 7 tested vaccine serotypes. This percentage rose to 54% after the second dose of PCV7 and did not increase further after PPV23. Over 90% of patients had antibody concentrations ≥ 1.0 µg/mL for at least 5 out of the 7 conjugated pneumococcal serotypes after 2 doses of PCV7. For serotypes, included in the PPV23 vaccine only, 25% (PPS3)-100% (PPS19A) of the patients reached antibody concentrations ≥ 1.0 µg/mL after one dose of PPV23. For Hib, 97% of the patients reached the threshold concentration of ≥ 1.0 µg/mL after one dose of vaccine. It can be concluded that the majority of asplenic patients had a sufficient response to conjugated vaccines against Streptococcus pneumoniae and Hib, reflected by a ≥ 1.0 µg/mL antibody response. Inclusion of conjugated pneumococcal polysaccharide vaccines might be of additional value in the vaccination schedule for asplenic patients because of their high immunogenicity.

Acute-phase responsiveness of mannose-binding lectin in community-acquired pneumonia is highly dependent upon MBL2 genotypes.

Mannose-binding lectin (MBL) is a pattern recognition receptor of the complement system and plays an important role in innate immunity. Whether or not MBL acts as an acute-phase response protein in infection has been an issue of extensive debate, because MBL responses have shown a high degree of heterogeneity. Single nucleotide polymorphisms (SNPs) in the promoter (wild-type Y versus X) and exon 1 (A versus 0) of the MBL2 gene can lead to MBL deficiency. This study investigated the influence of SNPs in the promoter and exon 1 of the MBL2 gene on the acute-phase responsiveness of MBL in 143 patients with community-acquired pneumonia. Acute-phase reactivity was observed only in MBL-sufficient genotypes (YA/YA, XA/YA, XA/XA and YA/0). In patients with wild-type exon 1 genotype A/A, positive acute-phase responses were associated with the presence of the YA haplotype and negative responses with its absence. Genotypes YA/0 and XA/XA produced equal levels of MBL in convalescence. In the acute phase, however, patients with genotype XA/XA displayed negative acute-phase responses more often than those with genotype YA/0. Correlation of MBL and C-reactive protein levels in the acute phase of pneumonia also depended upon the MBL2 genotype. In conclusion, acute-phase responsiveness of MBL was highly dependent upon the MBL2 genotype. These data suggest that heterogeneity in protein responses in the acute phase of disease should always be viewed in the light of possible influences of genetic differences in both structural and regulatory parts of the gene.

Vaccination coverage and awareness of infectious risks in patients with an absent or dysfunctional spleen in the Netherlands.

OBJECTIVE: To evaluate the current practice to prevent infections in patients with an absent or dysfunctional spleen in a part of the Netherlands. To measure serum antibody levels against Streptococcus pneumoniae and Haemophilus influenzae type b. DESIGN: Observational study of vaccination coverage by analysis of questionnaires and serum antibody levels. SETTING: Primary care practices in the Utrecht area of the Netherlands, catchment area 750,000 inhabitants, period 2006-2007. PARTICIPANTS: One hundred and thirty adult patients with an absent or dysfunctional spleen. MAIN OUTCOME MEASURES: Percentage of patients informed about infectious risks and aware of the timely use of antimicrobial prophylaxis. Vaccine coverage against S. pneumoniae, H. influenzae type b and Neisseria meningitidis. Levels of serum antibodies against S. pneumoniae and H. influenzae type b. RESULTS: Fifty-six patients (43%) have not received up-to-date information about the infectious risks associated with their condition; 65 patients (50%) are not aware of the need to contact a physician immediately in case of high fever; 37 patients (28%) are keeping antimicrobial prophylaxis at home. Pneumococcal vaccination has been administered within the last 5 years to 103 of 130 patients, antibody levels above the threshold of > or =0.35microg/mL are found in 83 of the 101 patients (data lacking in 2 patients). Complete coverage against S. pneumoniae is only 64% (83/130). A minority of patients (respectively 32% and 27%) has been vaccinated against H. influenzae type b and N. meningitidis. CONCLUSIONS: Vaccination coverage and education about infectious risks in patients with an absent or dysfunctional spleen can be improved markedly in the Netherlands.

Vaccination responses and lymphocyte subsets after autologous stem cell transplantation.

Twenty autologous stem cell transplant recipients were vaccinated with three doses of Diphtheria-Tetanus-Poliomyelitis vaccine and conjugated Haemophilus influenzae type b (Hib) vaccine. Pneumococcal vaccination consisted of two doses of conjugated vaccine followed by a single dose of polysaccharide vaccine, at 6, 8 and 14 months after transplantation, respectively. Mean anti-tetanus, anti-Hib and anti-pneumococcal IgG antibodies significantly increased after each vaccination. Response rates after the full vaccination schedule were 94%, 78% and 61% for Hib, conjugated 7-valent pneumococcal vaccine and non-conjugated 23-valent pneumococcal vaccine, respectively. Three months after transplantation, CD16(+)CD56(+) NK cells were in the normal range and remained so. The total number of T lymphocytes at 3 months was and remained in the normal range. The mean CD4/CD8 ratio was 0.43 at 3 months post aSCT and, while gradually increasing, remained subnormal. The mean number of CD19(+) B lymphocytes significantly increased during the study period. Patients with CD19 counts <0.10 x 10(9)L(-1) required at least two Hib vaccinations to show a response, while the majority of patients with CD19 counts > or = 0.20 x 10(9)L(-1) showed a response to Hib after one vaccination only. Thus, a minimum threshold level of CD19(+) cells appears to be required for adequate responses to vaccination.

Development of T cell-mediated immunity after autologous stem cell transplantation: prolonged impairment of antigen-stimulated production of gamma-interferon.

The conditioning regimens for autologous SCT (auto-SCT) lead to impairment of the immune system and concomitant increase in susceptibility to infections. We studied the recovery of cellular immunity by in vitro analysis of T-cell proliferation and cytokine production profiles during the first 15 months after auto-SCT in patients with multiple myeloma and non-Hodgkin's lymphoma. PBMC were collected at 6, 9 and 15 months after transplantation and stimulated with a combination of CD2 and CD28 monoclonal antibodies, with PHA or with tetanus toxoid as recall antigen. A multiplex enzyme linked immunoassay was used to determine levels of Th1 cytokines IL-2, IFN-gamma and tumour-necrosis factor-alpha (TNF-alpha), Th2 cytokines IL-4, IL-5 and IL-13, the regulatory cytokine IL-10 and the proinflammatory cytokines IL-1alpha, IL-1beta, IL-6 and the chemokine IL-8. T-cell proliferation progressively increased from 6 to 15 months after auto-SCT. Overall, cytokine production increased after auto-SCT. Production of Th2 cytokines IL-5 and IL-13 was superior to production of Th1 cytokines IFN-gamma and TNF-alpha. We hypothesize that prolonged impairment of IFN-gamma production might contribute to the relatively high incidence of viral infections after auto-SCT.

Impaired pneumococcal antibody response in bronchiectasis of unknown aetiology.

As a defective anti-polysaccharide response can exist in the absence of an immunoglobulin deficiency, a series of 26 patients with bronchiectasis of unknown aetiology was vaccinated with a 23-valent pneumococcal polysaccharide vaccine. All patients suffered from recurrent respiratory tract infections. When measuring total antibody levels to pneumococcal serotypes 3, 4 and 9, a normal polysaccharide antibody response was found in 22 patients. However, only 11 of these subjects showed a normal pneumococcal antibody response within the IgA and/or IgG2 subclass, and thus could be classified as true responders, while 15 patients did not respond in either the IgA class or in the IgG2 subclass. When analysing differences between the responder (n = 11) and nonresponder (n = 15) groups, the latter demonstrated higher frequencies of respiratory tract infections and more severe lung pathology, as revealed by the presence of more bronchi visualised in the peripheral third of the lung by high-resolution computed tomography scanning. Moreover, nonresponders needed extensive lung surgery more often in order to control their disease (number of resected segments eight versus five). In conclusion, an important fraction of patients presenting with idiopathic bronchiectasis is associated with a selective anti-polysaccharide response deficiency and this subgroup appears to represent a more severe clinical phenotype. Therefore, it can be regarded as a separate clinical entity with possible therapeutic targets. In order to identify IgA and IgG2 anti-polysaccharide nonresponders, all patients presenting with bronchiectasis of unknown aetiology should be immunised with a pneumococcal polysaccharide vaccine, and IgA and IgG2 isotype responses should be evaluated as well as the total antibody response.

Influenza virus vaccination and booster in B-cell chronic lymphocytic leukaemia patients.

Background: Influenza vaccination is recommended for patients with B-cell chronic lymphocytic leukaemia (CLL). Because response rates are often low, we decided to evaluate antibody response to single and booster vaccinations with influenza A and B virus vaccine in these patients. Methods: Twenty patients with B-CLL received two subunit virus vaccine injections 21 days apart. Antibody titres were determined before and 21 days after the single and booster vaccinations. The serological response was expressed using the following criteria: (1) response rate, i.e. the proportion of subjects with at least a 4-fold titre increase; (2) the protection rate, i.e. the proportion of subjects exceeding the threshold of 100 (influenza A) or 200 (influenza B); and (3) the mean fold increase (MFI), i.e. the difference between the log-adjusted geometric mean titres of pre- and post-vaccination sera. Results: Response rates were 5% for influenza A and 15% for B after the single vaccination and 15% for A and 30% for B after the booster vaccination. Protection rates were 0% for influenza A and 25% for B after the single vaccination; they were 5% (H1N1) and 10% (H3N2) for influenza A and 30% for B after the booster. The MFI+/-S.D. (range) after the booster vaccination was 0.26+/-0.33 (0-1.00), 0.17+/-0.34 (0-1.00) and 0.35+/-0.34 (0-1.20) for H1N1, H3N2 and influenza B, respectively. Conclusion: In this study with B-CLL patients, immune response to influenza vaccination was poor. Thus, single and booster vaccinations with influenza virus vaccine do not appear to be of great value to patients with B-cell CLL.

A family with complement factor D deficiency.

A complement factor D deficiency was found in a young woman who had experienced a serious Neisseria meningitidis infection, in a deceased family member with a history of meningitis, and in three relatives without a history of serious infections. The patient and these three relatives showed a normal activity of the classical complement pathway, but a very low activity of the alternative complement pathway and a very low capacity to opsonize Escherichia coli and N. meningitidis (isolated from the patient) for phagocytosis by normal human neutrophils. The alternative pathway-dependent hemolytic activity and the opsonizing capacity of these sera were restored by addition of purified factor D. The family had a high degree of consanguinity, and several other family members exhibited decreased levels of factor D. The gene encoding factor D was found to contain a point mutation that changed the TCG codon for serine 42 into a TAG stop codon. This mutation was found in both alleles of the five completely factor D-deficient family members and in one allele of 21 other members of the same family who had decreased or low-normal factor D levels in their serum. The gene sequence of the signal peptide of human factor D was also identified. Our report is the first, to our knowledge, to document a Factor D gene mutation. The mode of inheritance of factor D deficiency is autosomal recessive, in accordance with the localization of the Factor D gene on chromosome 19. Increased susceptibility for infections in individuals with a partial factor D deficiency is unlikely.

Antibody responses to pneumococcal and haemophilus vaccinations in patients with B-cell chronic lymphocytic leukaemia.

Although vaccination against Streptococcus pneumoniae (S. pneumoniae) and Haemophilus influenzae type b (Hib) is recommended for immunocompromised patients, such as patients with B-cell chronic lymphocytic leukaemia (B-CLL), its protective effect is questionable. We studied antibody responses to pneumococcal polysaccharide vaccine (Pneumovax-23) and to conjugated H. influenzae type b-vaccine (Act-Hib) in 25 patients with B-CLL. After vaccination, the number of patients with antibody levels in the protective range against pneumococcal serotypes and H. influenzae b increased from 9 (38%) to 12 (50%) of 24 patients and from 8 (35%) to 11 (48%) of 23 patients, respectively. The patients with adequate antibody response to Pneumovax-23 and Act-Hib had significantly less advanced stages of B-CLL, higher gammaglobulin levels, total IgG-levels and IgG-subclasses 2 and 4 levels, and lower levels of soluble CD23. Consequently, vaccination with these vaccines should be given as soon as the diagnosis of B-CLL is made, early in the course of the disease with determination of post-vaccination antibody levels.

Clinical and immunological evaluation of patients with mild IgG1 deficiency.

Serum IgG subclass concentrations were determined in patients visiting, the pulmonology out-patient clinic with chronic respiratory tract problems. A total of 24 patients with a serum IgG1 concentration < 4.9 g/l (i.e. below the reference range) and normal values for IgG2, IgM and IgA were included. Patients with a selective IgG1 deficiency were vaccinated with a 23-valent pneumococcal polysaccharide vaccine. There were nine patients with a poor antibody response to pneumococcal capsular polysaccharide antigens. Responsiveness to protein antigens was intact in all patients. Patients with pneumonia showed a significantly lower anti-polysaccharide response in the IgG2 subclass than patients without pneumonia. Patients with recurrent sinusitis showed a significantly lower response in the IgA isotype after vaccination with pneumococcal polysaccharide vaccine compared with non-sinusitis patients. It can be concluded that patients with recurrent sinopulmonary infections and a mild IgG1 subclass deficiency have an impaired IgG1 anti-polysaccharide response, which can extend to decreased IgG2 and IgA anti-polysaccharide responses.

Detection of immunoglobulins G and A to Aspergillus fumigatus by immunoblot analysis for monitoring Aspergillus-induced lung diseases.

The aim of the study was to investigate whether patients with Aspergillus-induced lung disease can be monitored by immunoblot analysis to detect antibodies to Aspergillus fumigatus (Af). Immunoblotting was performed by incubating 57 longitudinally collected sera from 13 patients on nitrocellulose sheets, blotted with Af antigen, separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Bound antibodies were demonstrated by peroxidase-labelled antihuman immunoglobulins (Ig)G and IgA antiserum and diaminobenzidine plus H2O2 as substrate. The immunoblot patterns were related to the patients' clinical status and time. Each patient had a characteristic immunoblot pattern that varied with time. There was a relationship between disease activity or clinical response and changes in immunoblot antibody patterns: a rise in anti-Af IgG and IgA antibodies was seen in sera collected during active disease, compared with before active disease, and a significant decline in anti-Af IgG and IgA was demonstrated in sera collected during recovery, compared with during active disease. Only in the acute stage of allergic bronchopulmonary aspergillosis were IgA antibodies against Af antigens of <20,000 Da demonstrated. Immunoblot analysis can be used to monitor the disease activity and the responses to treatment of patients with Aspergillus-induced lung diseases. Changes in specific immunoglobulin A may be more informative than specific immunoglobulin G.

Is the different T helper cell activity in sarcoidosis and extrinsic allergic alveolitis also reflected by the cellular bronchoalveolar lavage fluid profile?

BACKGROUND: Sarcoidosis is generally characterized by a CD4+ lymphocyte predominance in bronchoalveolar lavage fluid (BALF), whereas in extrinsic allergic alveolitis (EAA) a CD8+ lymphocyte predominance is found. However, we have previously demonstrated an increase in CD4+ lymphocytes in BALF obtained from EAA patients as well. The aim of this study was to evaluate whether in sarcoidosis and EAA the BALF cellular profile-even without the help of cytokine detection-might reflect differences in the CD4+ T-lymphocyte subpopulations, i.e. T helper (TH)-1 and TH2 lymphocytes. METHODS: For this purpose, we analyzed BALF analysis results obtained from 77 nonsmoking patients with histologically proven sarcoidosis and 54 nonsmoking patients suffering from EAA. RESULTS: Patients with EAA showed the highest mean absolute numbers of lymphocytes, CD8+ as well as CD4+ T lymphocytes, whereas the percentage of CD4+ T lymphocytes in BALF was low. In contrast, patients with sarcoidosis showed the lowest absolute and relative number of CD8+ T lymphocytes, the highest percentage of CD4+ T lymphocytes and CD4+/CD8+ ratio. Moreover, patients with Löfgren's syndrome demonstrated an alveolitis suggesting a TH1 lymphocyte-subset-like predominant related profile, characterized by lower numbers of eosinophils and mast cells, whereas sarcoidosis patients with respiratory symptoms formed a more mixed TH1/TH2 pattern. Patients with EAA showed a cellular BALF profile suggesting a functional predominance of TH2 lymphocytes. CONCLUSION: These preliminary data suggest a different distribution of the CD4+ T lymphocyte subtypes characterized by a functional heterogeneity of CD4+ T lymphocytes between-as well as within-these various pulmonary disorders. The exact role of this imbalance of TH1 and TH2-like activity in the lung with regard to the pathogenesis and prognosis needs to be further elucidated.

Eosinophil cationic protein and immunoglobulin levels in bronchoalveolar lavage fluid obtained from patients with chronic eosinophilic pneumonia.

In chronic eosinophilic pneumonia (CEP), histopathological evidence exists for the degranulation of eosinophils and the release of various toxic proteins. In vitro studies have demonstrated the degranulation of eosinophils in response to aggregated and complexed immunoglobulins. The aims of this study were to investigate: 1) whether the eosinophil cationic protein (ECP) and immunoglobulin (Ig) levels in bronchoalveolar lavage (BAL) fluid from patients with CEP are increased compared to those of healthy controls; 2) and whether a relationship is present between immunoglobulin levels and ECP levels in BAL fluid from patients with CEP. The BAL from 12 patients with CEP was selected, retrospectively, from all BAL analyses performed in our centre between 1986 and 1992. ECP levels were measured using a radioimmunoassay in BAL fluid of patients with CEP and 10 healthy controls. ECP levels and immunoglobulin levels in BAL fluid from patients with CEP were found to be elevated compared to controls (p < 0.001). A relationship was found between IgA levels and ECP levels in BAL fluid from patients with CEP (r = 0.72; p = 0.043). In conclusion, eosinophil cationic protein and immunoglobulin levels were found to be increased in bronchoalveolar lavage fluid from patients with chronic eosinophilic pneumonia. The relationship found between immunoglobulin A levels and eosinophil cationic protein levels may suggest that immunoglobulin A could be involved in the degranulation of eosinophils in chronic eosinophilic pneumonia.